Localized suppression of cortical growth hormone-releasing hormone receptors state-specifically attenuates electroencephalographic delta waves.

Growth hormone-releasing hormone (GHRH) promotes non-rapid eye movement sleep (NREMS), in part via a well characterized hypothalamic sleep-promoting site. However, GHRH may also act in the cortex to influence sleep. Application of GHRH to the surface of the cortex changes electroencephalographic (EEG) delta power. GHRH and the GHRH receptor (GHRHR) mRNAs are detectable in the rat cortex, and the expression of cortical GHRHR is activity dependent. Here, we microinjected a GHRH antagonist or GHRHR small interfering RNA (siGHRHR) onto the somatosensory cortex surface in rats. The unilateral application of the GHRH antagonist ipsilaterally decreased EEG delta wave power during NREMS, but not wakefulness, during the initial 40 min after injection. Similarly, the injection of siGHRHR reduced cortical expression of GHRHR and suppressed NREMS EEG delta wave power during 20-24 h after injection. Using the fura-2 calcium imaging technique, cultured cortical cells responded to GHRH by increasing intracellular calcium. Approximately 18% of the GHRH-responsive cells were GABAergic as illustrated by glutamic acid decarboxylase-67 (GAD67) immunostaining. Double labeling for GAD67 and GHRHR in vitro and in vivo indicated that only a minority of cortical GHRHR-containing cells were GABAergic. Our data suggest that endogenous cortical GHRH activates local cortical cells to affect EEG delta wave power state-specifically. Results are also consistent with the hypothesis that GHRH contributes to local network state regulation.

Developmental changes in the human sleep EEG during early adolescence.

STUDY OBJECTIVES: To use time-frequency analysis to characterize developmental changes in the human sleep electroencephalogram (EEG) across early adolescence. DESIGN: Sleep EEG was recorded when children were 9/10 years old and 1 to 3 years later after sleeping at home on a fixed schedule for at least one week. SETTING: A 4-bed sleep laboratory. PARTICIPANTS: Fourteen (5 girls) healthy children ages 9/10 (mean = 10.13, SD = +/- 0.51) years at initial and 11 to 13 (mean = 12.28, SD = +/- 0.62) years at follow-up. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All-night polysomnography was performed at each assessment and sleep stages were scored with Rechtschaffen and Kales criteria. Slow wave sleep minutes decreased from the initial to the follow-up session by 29%, while minutes of stage 2 increased by 17%. NREM and REM sleep EEG spectra from two central and two occipital leads were examined for developmental changes. All-night analyses showed a significant decrease of EEG power from the initial to follow-up session across a range of frequencies during NREM and REM sleep. This decline occurred across leads and states in the delta/theta bands (3.8 - 7 Hz). Time-frequency analyses indicated that this effect was consistent across the night. The decline in power with age was most pronounced in the left central and right occipital leads. The frequency of greatest power in the sigma band (11 - 16 Hz) was significantly higher at follow-up. CONCLUSIONS: This longitudinal analysis highlights asymmetrical frequency-specific declines in sleep EEG spectral power with early adolescent maturation, which may reflect early signs of the cortical synaptic pruning in the healthy adolescent.

Homeostatic sleep response to naps is similar in normal elderly and young adults.

Delta homeostatic regulation can be challenged by reducing delta need with daytime naps and measuring delta in post-nap sleep. We previously demonstrated that, after a late afternoon nap, young adults reduce the amount of delta in post-nap sleep by the amount in the nap. We compared homeostatic responses of 19 young adults (mean age 22.4 years) and 19 normal elderly subjects (mean age 71.4 years). Each participated in four separate 2-day sessions that consisted of a baseline night, a nap, and post-nap sleep. Nap times were 0900, 1200, 1500 and 1800 h. The 1800 h nap contained the largest amount of delta and produced the largest reduction in post-nap delta. The young and elderly groups respectively produced 28 and 24% of baseline delta in the 1800 h nap. Both groups showed equivalent delta regulation, reducing post-nap delta by 28 and 25%, respectively. In both age groups, the decrease in post-nap delta resulted from a reduced rate of delta production (power/min) and reduced non-rapid eye movement (NREM) sleep duration. Period-amplitude analysis showed that the reduction in power/min resulted from decreases in delta wave amplitude and incidence. None of the responses to nap challenges differed significantly across age groups nor were there gender differences or age by gender interactions. These results show that delta homeostatic responses to naps in the elderly parallel those of young subjects. REM sleep showed no homeostatic reductions following naps in either group. We believe that the striking differences in the delta and REM responses point to different biological roles of the two kinds of sleep.

High resolution parametric description of slow wave sleep.

We propose a new framework for quantitative analysis of sleep EEG, compatible with the traditional analysis, based upon adaptive time-frequency approximation of signals. Using a high resolution description of EEG rhythms and transients in terms of their time occurrence and width, frequency and amplitude, we present a detailed detection and parameterization of delta waves, including also the time occupied by each delta wave-a parameter inaccessible directly by previously applied signal processing methods. To validate the proposed parameterization, we construct a simple detector of sleep stages 3 and 4, based explicitly upon the classical criteria related to delta waves. To properly compare its performance to the inter-expert agreements and other expert systems, we sort out and discuss the methodology of reporting concordance in this context. Since the proposed parameterization proves to be compatible with the visual analysis of EEG, we can derive new variables for quantitative analysis of EEG patterns recognized for decades. As examples, we present a continuous description of delta waves and sleep spindles in the overnight sleep, and compare results to the traditional FFT-based estimates.

Progressive aging does not alter the interaction between autonomic cardiac activity and delta EEG power.

OBJECTIVE: We tested the hypothesis that the reductions of the changes in the respective influence of the cardiac sympathetic and vagal activity control and delta EEG activity with aging alter the interactions between the heart rate variability (HRV) and the delta sleep EEG power band. METHODS: A polysomnography was performed on 16 healthy young men and 19 healthy middle-aged men across the first 3 NREM-REM cycles. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. High Frequency (HF(nu)) of HRV as well as the maximum of cross-spectrum, coherency, gain and phase shifts between HF(nu) and delta sleep EEG power band were compared between both groups. RESULTS: Young men experienced more deep sleep than middle-aged men (P<0.001). In middle-aged subjects, HF(nu) was lower than the HF(nu) of their younger counterparts (P<0.001), but they showed similar increases during NREM sleep and similar decreases during REM sleep as the young subjects. Cross-spectrum values, coherency, gain and phase shifts between HF(nu) and delta were identical between the two groups. Modifications in HF(nu) show parallel changes and precede changes in delta EEG band by a similar leads of 11+/-6min in young men and 9+/-7 min in middle-aged men (P=0.23). CONCLUSIONS: Reduced changes in the respective influence of the cardiac sympathetic and vagal activity and delta EEG activity with progressive aging do not alter the relationship and phase difference between changes in the relative predominant cardiac vagal activity and delta power in middle-aged men. SIGNIFICANCE: Interaction between the cardiac sympathetic and vagal activity with delta EEG activity is maintained in middle-aged men.

Evaluation of a filter/integrator system for quantifying delta activity in the sleep electroencephalogram.

The integrated output of a delta bandpass filter was evaluated as a means of quantifying delta activity in the sleep electroencephalogram (EEG). Total integrated slow wave amplitude (ISWA) and a density measure (ISWA/20-s epoch) were determined from four complete NREM sleep periods (NREMPs) on each of 2 baseline nights from 15 subjects. Total ISWA displays a linear decline across NREMPs, whereas ISWA/20-s epoch shows a curvilinear decline. Both measures show highly significant correlations with manually staged slow wave sleep and a high degree of intra-individual consistency between nights, for both whole-night values and those of individual NREMPs. The slow-wave density index (ISWA/20-s epoch) demonstrated consistently higher between-night correlations across NREMPs than did the total ISWA index, particularly in the first NREMP, suggesting it may better characterize the nightly distribution of delta activity in an individual's sleep EEG.

Inverse coupling between ultradian oscillations in delta wave activity and heart rate variability during sleep.

OBJECTIVE: We investigate the relationship between changes in heart rate variability and electroencephalographic (EEG) activity during sleep. METHOD: Nine male subjects with regular non-rapid-eye movement-rapid-eye movement (NREM-REM) sleep cycles were included in the study. They underwent EEG and cardiac recordings during one experimental night. Heart rate variability was determined over 5-min periods by the ratio of low frequency to low frequency plus high frequency power [LF/(LF+HF)] calculated using spectral analysis of R-R intervals. EEG spectra were analyzed using a fast Fourier transform algorithm. RESULTS: We found an ultradian 80-120 min rhythm in the LF/(LF+HF) ratio, with high levels during rapid eye movement (REM) sleep and low levels during slow wave sleep (SWS). During sleep stage 2 there was a progressive decrease in the transition from REM sleep to SWS, and an abrupt increase from SWS to REM sleep. These oscillations were significantly coupled in a 'mirror-image' to the overnight oscillations in delta wave activity, which reflect sleep deepening and lightening. Cardiac changes preceded EEG changes by about 5 min. CONCLUSIONS: These findings demonstrate the existence of an inverse coupling between oscillations in delta wave activity and heart rate variability. They indicate a non-uniformity in sleep stage 2 that underlies ultradian sleep regulation.

The genesis of human event-related responses explained through the theory of oscillatory neural assemblies.

The goal of the study is to investigate the contribution of delta and theta responses to N200 and P300 ERP components that are recorded from two topographical sites (Fz and Pz) under two experimental paradigms (mismatch negativity and oddball) that trigger different cognitive processes for the respective task performances. The present study was conducted on 42 normal young adults. The results showed that it is the 'interplay' between the theta and the delta oscillations that produces the morphology and the amplitude not only of the P300 but also the N200 component. The functional and physiological meaning of the delta and theta responses are discussed within the framework of the theory of oscillatory neural assemblies and the principle of superposition.

Rapid eye movement density shows trends across REM periods but is uncorrelated with NREM delta in young and elderly human subjects.

Saccade-like eye movements are the most prominent phasic component of rapid eye movement (REM) sleep. Eye movement density (EMD) appears to be negatively related to sleep depth. Thus, EMD is depressed by sleep deprivation. We sought to determine in 19 young normal (YN) and 19 elderly normal (EN) subjects: (a) whether EMD is correlated with delta EEG in baseline sleep; (b) whether EMD is increased by daytime naps; and (c) whether EMD patterns across sleep cycles differ in the two age groups. Subjects participated in four separate 2-day recording sessions, each consisting of a baseline night, a daytime nap, and post nap night. EMD was measured as 0.3-2 Hz integrated amplitude (IA)/20 s stage REM. EMD was not correlated with rate of non rapid eye movement (NREM) delta production (power/min) in the baseline sleep of either group. Changes in EMD and delta power/min on post nap nights also were uncorrelated. These data indicate that very strong changes in sleep depth (state) are required to overcome the individual stability (traits) of NREM delta and eye movement density. ANOVA for EMD across REM periods 1-4 showed a significant cycle effect and a significant age x cycle interaction. These effects were mainly due to YNs having depressed EMD in the first REM period, likely due to the low arousal level early in sleep in these subjects. Compared with waking saccades the saccade eye movements of REM sleep have received little investigation. Further study of these movements could shed new light on neurophysiology of REM sleep. Such studies might also be clinically useful because the density of these movements appears to be related to depression and (independently) to cognitive function in individuals with brain impairment.

Distribution of epileptiform discharges during nREM sleep in the CSWSS syndrome: relationship with sigma and delta activities.

PURPOSE: The EEG pattern of epilepsy with continuous spike-waves during slow wave sleep (CSWSS) is characterized by an almost continuous activation of spike-and-slow-wave complexes during nREM sleep with a marked reduction of EEG abnormalities during REM sleep and the awake state. Experimental studies indicate that normal sleep oscillations that during nREM sleep lead to the appearance of spindles and delta waves on scalp EEG might develop into paroxysmal synchronization. Spectral analysis enables the quantitative description of the dynamics of delta (Delta Activity, DA, 0.5-4.5 Hz) and sigma activity (SA, 12-16 Hz) and can be used to assess the relationship between SA, DA and epileptiform discharges (EDs) during sleep. METHODS: We analyzed the EDs distribution during sleep in five children affected by CSWSS. We used a model of the evolution of power of DA and SA to which the time series of EDs could be fitted. RESULTS: We found a high and positive correlation between EDs and SA. DA resulted negatively correlated with EDs. CONCLUSION: Our data suggest that neural mechanisms involved in the generation of sleep spindles facilitate EDs production in the CSWSS syndrome. Such a mechanism seems to be an age related phenomenon shared by other epileptic syndromes of childhood.

Neuroprotection assessment by topographic electroencephalographic analysis: effects of a sodium channel blocker to reduce polymorphic delta activity following ischaemic brain injury in rats.

The spatiotemporal electroencephalogram (EEG) pathology associated with brain injury was studied using high-resolution, 10-electrode cortical EEG mapping in a rat model of middle cerebral artery occlusion (MCAo). Using this model we evaluated the ability of the novel sodium channel blocker and neuroprotective agent RS100642 to resolve injury-induced EEG abnormalities as a measure of neurophysiological recovery from brain injury. The middle cerebral artery (MCA) was occluded for 1 h during which a dramatic loss of EEG power was measured over the injured cortex with near complete recovery upon reperfusion of blood to the MCA region in all rats. The resultant progression of the MCAo/reperfusion injury (6-72 h) included the appearance of diffuse polymorphic delta activity (PDA), as visually indicated by the presence of high-amplitude slow-waves recorded from both brain hemispheres. PDA was associated with large increases in EEG power, particularly evident in outer 'peri-infarct' regions of the ipsilateral parietal cortex as visualized using topographic EEG mapping. Post-injury treatment with RS100642 (1.0 mg/kg, i.v.) significantly reduced the PDA activity and attenuated the increase in EEG power throughout the course of the injury. These effects were associated with a reduction in brain infarct volume and improved neurological function. These methods of EEG analysis may be helpful tools to evaluate the physiological recovery of the brain from injury in humans following treatment with an experimental neuroprotective compound.

Resting state eyes-closed cortical rhythms in patients with locked-in-syndrome: an EEG study.

OBJECTIVE: Locked-in syndrome (LIS) is a state of complete paralysis, except for ocular movements, which results from ventral brainstem lesions. Patients typically are fully conscious. Here we tested the hypothesis that electroencephalographic (EEG) rhythms are abnormal in LIS patients, possibly due to an impaired neural synchronization between brainstem and cerebral cortex. METHODS: Resting state eyes-closed EEG data were recorded in 13 LIS subjects and 15 cognitively normal control subjects. With reference to the individual alpha frequency (IAF), the bands of interest were delta (IAF-8 to IAF-6Hz), theta (IAF-6 to IAF-4Hz), alpha 1 (IAF-4 to IAF-2Hz), alpha 2 (IAF-2 to IAFHz), and alpha 3 (IAF to IAF+2Hz). Furthermore, beta 1 (13-20Hz) and beta 2 (20-30Hz) bands were also considered. Cortical EEG sources were estimated by low-resolution electromagnetic tomography (LORETA). RESULTS: The power of alpha 2 and alpha 3 sources in all regions was lower in patients with LIS compared to controls. The power of delta sources in central, parietal, occipital and temporal regions was higher in patients with LIS compared to controls. CONCLUSIONS: These results suggest that cortical sources of resting state eyes-closed alpha and delta rhythms are abnormal in LIS patients. SIGNIFICANCE: LIS is accompanied by a functional impairment of cortical neuronal synchronization mechanisms in the resting state condition.

[Methods of localization of equivalent EEG sources in the diagnostics of protracted loss of consciousness].

Results of EEG study of patients in a protracted unconscious state due to severe cranial trauma using different methods of source localization (independent component analysis, the LORETA method) are presented in order to compare their diagnostic value. Also the results of the study of somatosensory evoked potentials (SSEP) to median nerve stimulation of and EEG are compared. The independent higher frequency components of the EEG power spectrum had the higher activity in the delta-band, were localized predominantly in the frontal brain hemispheres (frontal, temporal regions), positively correlated with pathological neurodynamic SSEP changes (r=0,69; p=0,003) and negatively with the scores on the Glasgow outcome scale (r=-0,66; p=0,005).

Rhythmic diffuse delta frequency activity presenting as an unusual EEG correlate of nonconvulsive status epilepticus: three case studies.

We report three cases of nonconvulsive status epilepticus (NCSE) in which electroencephalograms (EEGs) were dominated by rhythmic or semirhythmic, high-voltage, diffuse, delta activity. These recordings initially contained little or no clear epileptiform activity. Two of these patients had prolonged episodes of NCSE, which were recorded with continuous long-term EEGs. These recordings revealed focal epileptiform discharges as well as persistent generalized epileptiform patterns. Rhythmic or semirhythmic, diffuse, delta activity with little or no clear epileptiform components has only rarely been reported with NCSE. Diffuse delta slowing is commonly seen in many toxic-metabolic encephalopathies, and this activity may occasionally appear rhythmic. EEG and clinical characteristics that may help distinguish these conditions are discussed.

Delta waves differently modulate high frequency components of EEG oscillations in various unconsciousness levels.

In this paper we investigate the modulation properties of high frequency EEG activities by delta waves during various depth of anesthesia. We show that slow and fast delta waves (0-2 Hz and 2-4 Hz respectively) and high frequency components of the EEG (8-20 Hz) are correlated with each other and there is a kind of phase locking between them that varies with depth of anesthesia. Our analyses show that maximum amplitudes of high frequency components of the EEG signal are appeared in different phases of slow and fast delta waves when the concentration of Desflurane and Propofol anesthetic agents varies in a patient. There are some slight differences in using slow and fast components of delta waves. For instance, when depth of anesthesia changes, biphasic responses of the EEG have more influences on results of the fast delta wave method. In addition, this method obtains more robust and less noisy results compared with the slow delta wave method. Since phase angle between fast EEG oscillations and delta waves indicates the status of information processing in the brain and it changes in various unconsciousness levels, it may improve the performance of other classic methods of determining depth of anesthesia.

Magnetoencephalographic analysis of cortical oscillatory activity in patients with brain tumors: Synthetic aperture magnetometry (SAM) functional imaging of delta band activity.

Abnormal focal slow wave activity on electroencephalography and magnetoencephalography (MEG) is often seen in patients with various brain pathologies and MEG is capable of localizing cortical oscillatory activity with enhanced accuracy. In addition, MEG with synthetic aperture magnetometry (SAM) can depict changes in cortical oscillatory activity tomographically. Using SAM, we recorded cortical rhythms in patients with a brain tumor and evaluated the tomographic appearance of focal slow wave activity in relation to clinical signs and symptoms. Spontaneous MEG recordings were obtained in 15 patients with brain tumors. Statistically-determined power distributions in the delta-, theta-, and alpha-frequency bands were displayed tomographically and overlaid on individual magnetic resonance images. The location, strength and volume of enhanced activity were analyzed. Delta and theta band activities were significantly more intense in the cortex adjacent to tumors and in the surrounding edematous cortical areas than in other portions of the cortex. In 13 of the 15 patients, spatial distribution of enhanced focal delta activity coincided with the area responsible for the presenting signs and symptoms. Volumetric analysis revealed that emergence of tumor-related focal delta band activity in the cortex adjacent to a tumor, or with peritumoral edema, was greater for intra-axial tumors involving subcortical fibers than for extra-axial tumors. Patients with an increased volume of enhanced delta activity exhibited poor recovery of function in the early postoperative period. It is concluded that SAM imaging of focal delta activity can reveal functional alterations in cortical activity in patients with brain tumors and is useful for assessing cortical states associated with the existing pathology.

Classic electroencephalographic parameters: median frequency, spectral edge frequency etc.

Even today many anaesthesiologists rely on parameters of the autonomic nervous system, such as blood pressure and heart rate to decide if a patient is adequately anaesthetized. It is thought that the electroencephalogram (EEG) may provide more information on the state of anaesthesia. Because full EEG analysis is not possible in the operating room, processed EEG parameters have been developed comprising complex information into a single value. Time and frequency domain parameters are calculated. The power spectrum results from a Fourier analysis and can be described by parameters such as median frequency, spectral edge frequency and others. It was noted, however, that anaesthetics at low doses increase frequency of the EEG, whereas at high doses the EEG is depressed. This biphasic response makes it difficult to clearly distinguish the exact anaesthetic state of a patient. Median frequency and spectral edge frequency have been studied in numerous studies. However, no sole indicator has been derived from the EEG that could serve as a descriptor of anaesthetic depth.

Human thalamic medial pulvinar nucleus is not activated during paradoxical sleep.

Wakefulness and paradoxical sleep (PS) share a similar electrophysiological trait, namely, a more elevated level of high-frequency activities at both thalamic and cortical levels relative to slow wave sleep (SWS). The spatio-temporal binding of these high-frequency activities within thalamo-cortical networks is presumed to generate cognitive experiences during wakefulness. Similarly during PS, this phenomenon could be at the origin of the perceptual experiences forming dreams. However, contents of dreams often present some bizarre features which depart from our cognitive experiences in waking. This suggests some differences in processing and/or integration of brain activities during waking and PS. Using intracranial recordings in epileptic patients we observed, specifically during PS, the presence of unexpected delta frequency oscillations, as well as a surprisingly low amount of high-frequency activities, in a posterior region of the thalamus, the medial pulvinar nucleus (PuM). This discrepancy between activities in a thalamic nucleus and its related cortical areas may compromise the spatio-temporal binding of the high-frequency activities, resulting in altered perceptual experiences during dream periods.

The frontal predominance in human EEG delta activity after sleep loss decreases with age.

Sleep loss has marked and selective effects on brain wave activity during subsequent recovery sleep. The electroencephalogram (EEG) responds to sleep deprivation with a relative increase in power density in the delta and theta range during non-rapid eye movement sleep. We investigated age-related changes of the EEG response to sleep deprivation along the antero-posterior axis (Fz, Cz, Pz, Oz) under constant routine conditions. Both healthy young (20-31 years) and older (57-74 years) participants manifested a significant relative increase in EEG power density in the delta and theta range after 40 h of sleep deprivation, indicating a sustained capacity of the sleep homeostat to respond to sleep loss in ageing. However, the increase in relative EEG delta activity (1.25-3.75 Hz) following sleep deprivation was significantly more pronounced in frontal than parietal brain regions in the young, whereas such a frontal predominance was diminished in the older volunteers. This age-related decrease of frontal delta predominance was most distinct at the beginning of the recovery sleep episode. Furthermore, the dissipation of homeostatic sleep pressure during the recovery night, as indexed by EEG delta activity, exhibited a significantly shallower decline in the older group. Activation of sleep regulatory processes in frontal brain areas by an extension of wakefulness from 16 to 40 h appears to be age-dependent. These findings provide quantitative evidence for the hypothesis that frontal brain regions are particularly vulnerable to the effects of elevated sleep pressure ('prefrontal tiredness') and ageing ('frontal ageing').